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Random point mutati...
Random point mutations with major effects on protein-coding genes are the driving force behind premature aging in mtDNA mutator mice.
- Article/chapterEnglish2009
Publisher, publication year, extent ...
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Elsevier BV,2009
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:su-32931
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https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-32931URI
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https://doi.org/10.1016/j.cmet.2009.06.010DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:119147407URI
Supplementary language notes
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Language:English
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Summary in:English
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Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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The mtDNA mutator mice have high levels of point mutations and linear deletions of mtDNA causing a progressive respiratory chain dysfunction and a premature aging phenotype. We have now performed molecular analyses to determine the mechanism whereby these mtDNA mutations impair respiratory chain function. We report that mitochondrial protein synthesis is unimpaired in mtDNA mutator mice consistent with the observed minor alterations of steady-state levels of mitochondrial transcripts. These findings refute recent claims that circular mtDNA molecules with large deletions are driving the premature aging phenotype. We further show that the stability of several respiratory chain complexes is severely impaired despite normal synthesis of the corresponding mtDNA-encoded subunits. Our findings reveal a mechanism for induction of aging phenotypes by demonstrating a causative role for amino acid substitutions in mtDNA-encoded respiratory chain subunits, which, in turn, leads to decreased stability of the respiratory chain complexes and respiratory chain deficiency.
Subject headings and genre
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Shabalina, IrinaStockholms universitet,Avdelningen för fysiologi(Swepub:su)chaba
(author)
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Camara, Yolanda
(author)
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Wredenberg, AnnaKarolinska Institutet
(author)
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Calvaruso, Maria Antonietta
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Nijtmans, Leo
(author)
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Nedergaard, JanStockholms universitet,Avdelningen för fysiologi(Swepub:su)neder
(author)
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Cannon, BarbaraStockholms universitet,Avdelningen för fysiologi(Swepub:su)canno
(author)
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Larsson, Nils-GöranKarolinska Institutet
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Trifunovic, AleksandraKarolinska Institutet
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Stockholms universitetAvdelningen för fysiologi
(creator_code:org_t)
Related titles
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In:Cell metabolism: Elsevier BV10:2, s. 131-81932-74201550-4131
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- By the author/editor
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Edgar, Daniel
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Shabalina, Irina
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Camara, Yolanda
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Wredenberg, Anna
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Calvaruso, Maria ...
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Nijtmans, Leo
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show more...
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Nedergaard, Jan
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Cannon, Barbara
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Larsson, Nils-Gö ...
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Trifunovic, Alek ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Physiology
- Articles in the publication
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Cell metabolism
- By the university
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Stockholm University
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Karolinska Institutet